EP2970218B8 - Inhibiteurs d'adn-pk - Google Patents

Inhibiteurs d'adn-pk Download PDF

Info

Publication number
EP2970218B8
EP2970218B8 EP14719434.4A EP14719434A EP2970218B8 EP 2970218 B8 EP2970218 B8 EP 2970218B8 EP 14719434 A EP14719434 A EP 14719434A EP 2970218 B8 EP2970218 B8 EP 2970218B8
Authority
EP
European Patent Office
Prior art keywords
inhibitors
dna
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP14719434.4A
Other languages
German (de)
English (en)
Other versions
EP2970218A1 (fr
EP2970218B1 (fr
Inventor
John Patrick MAXWELL
Paul S. Charifson
Qing Tang
Steven M. Ronkin
Katrina Lee JACKSON
Albert Charles PIERCE
David J. Lauffer
Pan Li
Simon Giroux
Jinwang Xu
Mark A. Morris
John J. Court
Kevin M. Cottrell
Hongbo Deng
Nathan D. Waal
Wenxin Gu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Vertex Pharmaceuticals Inc
Original Assignee
Vertex Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to PL18207382T priority Critical patent/PL3527563T3/pl
Priority to MEP-2019-55A priority patent/ME03336B/fr
Application filed by Vertex Pharmaceuticals Inc filed Critical Vertex Pharmaceuticals Inc
Priority to RS20190243A priority patent/RS58374B1/sr
Priority to EP21192836.1A priority patent/EP3985003B1/fr
Priority to DK18207382.5T priority patent/DK3527563T3/da
Priority to EP18207382.5A priority patent/EP3527563B1/fr
Priority to SI201431104T priority patent/SI2970218T1/sl
Priority to PL14719434T priority patent/PL2970218T3/pl
Publication of EP2970218A1 publication Critical patent/EP2970218A1/fr
Publication of EP2970218B1 publication Critical patent/EP2970218B1/fr
Priority to HRP20190373TT priority patent/HRP20190373T1/hr
Application granted granted Critical
Publication of EP2970218B8 publication Critical patent/EP2970218B8/fr
Priority to CY20211101051T priority patent/CY1125436T1/el
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/08—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5386—1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40—Benzopyrazines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40—Benzopyrazines
    • C07D241/42—Benzopyrazines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40—Benzopyrazines
    • C07D241/44—Benzopyrazines with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/12—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/40—Heterocyclic compounds containing purine ring systems with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D475/00—Heterocyclic compounds containing pteridine ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems
EP14719434.4A 2013-03-12 2014-03-12 Inhibiteurs d'adn-pk Active EP2970218B8 (fr)

Priority Applications (10)

Application Number Priority Date Filing Date Title
PL14719434T PL2970218T3 (pl) 2013-03-12 2014-03-12 Inhibitory DNA-PK
RS20190243A RS58374B1 (sr) 2013-03-12 2014-03-12 Inhibitori dnk-pk
MEP-2019-55A ME03336B (fr) 2013-03-12 2014-03-12 Inhibiteurs d'adn-pk
DK18207382.5T DK3527563T3 (da) 2013-03-12 2014-03-12 Dna-pk-inhibitorer
EP18207382.5A EP3527563B1 (fr) 2013-03-12 2014-03-12 Inhibiteurs d'adn-pk
SI201431104T SI2970218T1 (sl) 2013-03-12 2014-03-12 DNA-PK inhibitorji
PL18207382T PL3527563T3 (pl) 2013-03-12 2014-03-12 Inhibitory DNA-PK
EP21192836.1A EP3985003B1 (fr) 2013-03-12 2014-03-12 Inhibiteurs d'adn-pk
HRP20190373TT HRP20190373T1 (hr) 2013-03-12 2019-02-26 Inhibitori dnk-pk
CY20211101051T CY1125436T1 (el) 2013-03-12 2021-12-01 Αναστολεις dna-pk

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201361777816P 2013-03-12 2013-03-12
PCT/US2014/024767 WO2014159690A1 (fr) 2013-03-12 2014-03-12 Inhibiteurs d'adn-pk

Related Child Applications (3)

Application Number Title Priority Date Filing Date
EP18207382.5A Division EP3527563B1 (fr) 2013-03-12 2014-03-12 Inhibiteurs d'adn-pk
EP18207382.5A Division-Into EP3527563B1 (fr) 2013-03-12 2014-03-12 Inhibiteurs d'adn-pk
EP21192836.1A Division EP3985003B1 (fr) 2013-03-12 2014-03-12 Inhibiteurs d'adn-pk

Publications (3)

Publication Number Publication Date
EP2970218A1 EP2970218A1 (fr) 2016-01-20
EP2970218B1 EP2970218B1 (fr) 2018-11-28
EP2970218B8 true EP2970218B8 (fr) 2019-04-10

Family

ID=50549437

Family Applications (3)

Application Number Title Priority Date Filing Date
EP21192836.1A Active EP3985003B1 (fr) 2013-03-12 2014-03-12 Inhibiteurs d'adn-pk
EP14719434.4A Active EP2970218B8 (fr) 2013-03-12 2014-03-12 Inhibiteurs d'adn-pk
EP18207382.5A Active EP3527563B1 (fr) 2013-03-12 2014-03-12 Inhibiteurs d'adn-pk

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EP21192836.1A Active EP3985003B1 (fr) 2013-03-12 2014-03-12 Inhibiteurs d'adn-pk

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP18207382.5A Active EP3527563B1 (fr) 2013-03-12 2014-03-12 Inhibiteurs d'adn-pk

Country Status (26)

Country Link
US (11) US9340557B2 (fr)
EP (3) EP3985003B1 (fr)
JP (2) JP6360878B2 (fr)
KR (1) KR102216284B1 (fr)
CN (2) CN107200749B (fr)
AU (2) AU2014244555B2 (fr)
BR (1) BR112015021888B1 (fr)
CA (1) CA2904641C (fr)
CY (2) CY1121360T1 (fr)
DK (2) DK2970218T3 (fr)
ES (2) ES2900061T3 (fr)
HK (1) HK1220190A1 (fr)
HR (2) HRP20211855T1 (fr)
HU (2) HUE057527T2 (fr)
IL (1) IL241330B (fr)
LT (2) LT2970218T (fr)
ME (1) ME03336B (fr)
MX (1) MX365294B (fr)
PL (2) PL3527563T3 (fr)
PT (2) PT3527563T (fr)
RS (2) RS62649B1 (fr)
RU (1) RU2676259C2 (fr)
SG (1) SG11201507203RA (fr)
SI (2) SI2970218T1 (fr)
TR (1) TR201901886T4 (fr)
WO (1) WO2014159690A1 (fr)

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SI2841428T1 (sl) 2012-04-24 2018-12-31 Vertex Pharmaceuticals Incorporated Inhibitorji DNA-PK
CN107200749B (zh) 2013-03-12 2019-09-03 沃泰克斯药物股份有限公司 Dna-pk抑制剂
EP3057953B1 (fr) 2013-10-17 2018-08-15 Vertex Pharmaceuticals Incorporated Co-cristaux de (s)-n-méthyl-8-(1-((2'-méthyl-[4,5'-bipyrimidin]-6-yl)amino)propan-2-yl)quinoline-4-carboxamide et leurs dérivés deutérés utilisés comme inhibiteurs de protéine kinase dépendante de l'adn (dna-pk)
EP3247701B1 (fr) 2015-01-20 2021-09-22 Boehringer Ingelheim Animal Health USA Inc. Composés anthelmintiques, compositions et leur procédé d'utilisation
MY190895A (en) * 2015-01-23 2022-05-18 Glaxosmithkline Ip Dev Ltd Pyrazolo [3,4-d] pyrimidin derivative and its use for the treatment of leishmaniasis
AU2017275657B2 (en) 2016-06-02 2021-08-19 Novartis Ag Potassium channel modulators
TW201815418A (zh) 2016-09-27 2018-05-01 Vertex Pharma 使用dna破壞劑及dna-pk抑制劑之組合治療癌症的方法
SI3571193T1 (sl) 2017-01-23 2022-04-29 Cadent Therapeutics, Inc. Modulatorji kalijevega kanalčka
CN107158001A (zh) * 2017-03-29 2017-09-15 解益新 一种治疗哮喘的药物组合物
ES2940786T3 (es) * 2018-01-17 2023-05-11 Vertex Pharma Compuestos de quinoxalinona, composiciones, métodos y kits para aumentar la eficiencia de edición del genoma
EP3740479A1 (fr) * 2018-01-17 2020-11-25 Vertex Pharmaceuticals Incorporated Inhibiteurs d'adn-pk
CN111757876B (zh) * 2018-01-17 2024-03-22 沃泰克斯药物股份有限公司 Dna-pk抑制剂
MA54758A (fr) 2019-01-18 2022-04-27 Astrazeneca Ab Inhibiteurs de pcsk9 et leurs procédés d'utilisation
CN111909147B (zh) * 2019-05-10 2021-07-20 山东轩竹医药科技有限公司 Dna-pk抑制剂
TW202110849A (zh) * 2019-05-27 2021-03-16 大陸商迪哲（江蘇）醫藥股份有限公司 Ｄｎａ依賴性蛋白激酶抑制劑
KR20220070443A (ko) 2019-08-27 2022-05-31 버텍스 파마슈티칼스 인코포레이티드 반복성 dna와 연관된 장애의 치료용 조성물 및 방법
CA3150516A1 (fr) * 2019-09-11 2021-03-18 Provincial Health Services Authority Composes inhibiteurs de l'adn-pk
EP4045506A4 (fr) * 2019-10-15 2023-08-30 Aucentra Therapeutics Pty Ltd Dérivés de 4-(imidazo[1,2-a] pyridin-3-yl)-n-(pyridin-3-yl)pyrimidin-2-amine pour le traitement de maladies et d'affections prolifératives
BR112022008000A2 (pt) * 2019-11-21 2022-07-12 Jiangsu Hengrui Medicine Co Derivado de pirazol-heteroarila, método de preparação para o mesmo e uso médico do mesmo
WO2021136462A1 (fr) * 2019-12-31 2021-07-08 成都百裕制药股份有限公司 Dérivés furane et leur application en médecine
CN113121573A (zh) * 2019-12-31 2021-07-16 成都百裕制药股份有限公司 嘌呤衍生物及其在医药上的应用
EP4143304A2 (fr) 2020-04-28 2023-03-08 Intellia Therapeutics, Inc. Procédés d'administration de cellules in vitro
EP4217357A1 (fr) * 2020-09-24 2023-08-02 Auckland Uniservices Limited Nouvelles aminopyridines et leur utilisation dans le traitement du cancer
IL305307A (en) * 2021-02-19 2023-10-01 Kalvista Pharmaceuticals Ltd Factor XIIA inhibitors
EP4298222A1 (fr) 2021-02-26 2024-01-03 Vertex Pharmaceuticals Incorporated Compositions et méthodes de traitement de la dystrophie myotonique de type 1 avec crispr/sacas9
WO2022182959A1 (fr) 2021-02-26 2022-09-01 Vertex Pharmaceuticals Incorporated Compositions et méthodes pour le traitement de la dystrophie myotonique de type 1 avec crispr/slucas9
CA3213120A1 (fr) * 2021-03-10 2022-09-15 adMare Therapeutics Society Derives 7-morpholino-1,6-naphtyridin-5-yle et leurs compositions pharmaceutiques utiles en tant qu'inhibiteur de l'adn-pk
KR20240017791A (ko) 2021-04-17 2024-02-08 인텔리아 테라퓨틱스, 인크. Dna-의존적 단백질 키나제의 억제제 및 이의 조성물 및 용도
WO2023018637A1 (fr) 2021-08-09 2023-02-16 Vertex Pharmaceuticals Incorporated Édition génique d'éléments régulateurs

Family Cites Families (175)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5571506A (en) 1989-08-14 1996-11-05 Rhone-Poulenc Rorer Pharmaceuticals Inc. Aromatic oligomeric compounds useful as mimics of bioactive macromolecules
JPH05503517A (ja) 1989-12-18 1993-06-10 バージニア・コモンウェルス・ユニバーシティ シグマレセプターリガンド及びその用途
ATE156120T1 (de) 1991-02-07 1997-08-15 Roussel Uclaf Bizyklische stickstoffverbindungen, ihre herstellung, erhaltene zwischenprodukte, ihre verwendung als arzneimittel und diese enthaltende pharmazeutische zusammensetzungen
US6004979A (en) 1991-02-07 1999-12-21 Hoechst Marion Roussel Nitrogenous bicycles
EP0519211A1 (fr) 1991-05-17 1992-12-23 Hoechst Schering AgrEvo GmbH 4-Aminopyrimidines substituées, procédé pour leur préparation et leur utilisation comme parasiticide
DE4208254A1 (de) 1992-03-14 1993-09-16 Hoechst Ag Substituierte pyrimidine, verfahren zu ihrer herstellung und ihre verwendung als schaedlingsbekaempfungsmittel und fungizid
WO1993022291A1 (fr) 1992-04-24 1993-11-11 E.I. Du Pont De Nemours And Company Aminopyrimidines arthropidicides et fongicides
US5595756A (en) 1993-12-22 1997-01-21 Inex Pharmaceuticals Corporation Liposomal compositions for enhanced retention of bioactive agents
DE4437406A1 (de) 1994-10-19 1996-04-25 Hoechst Ag Chinoxaline, Verfahren zu ihrer Herstellung und ihre Verwendung
US5977117A (en) 1996-01-05 1999-11-02 Texas Biotechnology Corporation Substituted phenyl compounds and derivatives thereof that modulate the activity of endothelin
EP0968206B8 (fr) 1997-02-19 2007-01-24 Berlex, Inc. Derives n-heterocycliques utiles en tant qu'inhibiteurs de la no synthetase
JPH10251255A (ja) 1997-03-14 1998-09-22 Nissan Chem Ind Ltd アジン誘導体
WO1998054156A1 (fr) * 1997-05-28 1998-12-03 Rhone-Poulenc Rorer Pharmaceuticals, Inc. COMPOSES QUINOLINE ET QUINOXALINE INHIBANT LE FACTEUR DE CROISSANCE DERIVE DES PLAQUETTES ET/OU LES TYROSINE-KINASES P56?lck¿
DE19801598C2 (de) 1998-01-17 2000-05-11 Aventis Res & Tech Gmbh & Co Katalytische Synthese von N-alkylierten Anilinen aus Olefinen und Anilinen
DE19836697A1 (de) 1998-08-13 2000-02-17 Hoechst Marion Roussel De Gmbh Substituierte 4-Amino-2-aryl-pyrimidine, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate
EP1147094A1 (fr) 1999-01-15 2001-10-24 Novo Nordisk A/S Agonistes non peptidiques de glp-1
WO2001025220A1 (fr) 1999-10-07 2001-04-12 Amgen Inc. Inhibiteurs de triazine kinase
GB9924092D0 (en) 1999-10-13 1999-12-15 Zeneca Ltd Pyrimidine derivatives
US6552016B1 (en) 1999-10-14 2003-04-22 Curis, Inc. Mediators of hedgehog signaling pathways, compositions and uses related thereto
WO2001057021A2 (fr) 2000-02-01 2001-08-09 Cor Therapeutics, Inc. 2-[1H]-QUINOLONE ET 2-[1H]-QUINOXALONE INHIBITEURS DU FACTEUR Xa
DE60115394T2 (de) 2000-02-29 2006-10-19 Millennium Pharmaceuticals, Inc., Cambridge Benzamide und ähnliche inhibitoren vom faktor xa
AU2001245401A1 (en) 2000-03-01 2001-09-12 Sumitomo Pharmaceuticals Company, Limited Hydrazones and analogs as cholesterol lowering agents
DE10013318A1 (de) 2000-03-17 2001-09-20 Merck Patent Gmbh Formulierung enthaltend Chinoxalinderivate
US7498304B2 (en) 2000-06-16 2009-03-03 Curis, Inc. Angiogenesis-modulating compositions and uses
EP1351946A2 (fr) 2000-09-01 2003-10-15 Icos Corporation Substances potentialisant un traitement anticancereux et methodes a cet effet
US6660731B2 (en) 2000-09-15 2003-12-09 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
US6613776B2 (en) 2000-09-15 2003-09-02 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
US6610677B2 (en) 2000-09-15 2003-08-26 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
EP1317449B1 (fr) 2000-09-15 2006-05-31 Vertex Pharmaceuticals Incorporated Composes de pyrazole utiles comme inhibiteurs de proteine kinase
US7473691B2 (en) 2000-09-15 2009-01-06 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
CA2430539C (fr) 2000-12-05 2010-07-13 Vertex Pharmaceuticals Incorporated Inhibiteurs de kinases c-jun n-terminales (jnk) et d'autres proteines kinases
ES2265450T3 (es) 2000-12-21 2007-02-16 Vertex Pharmaceuticals Incorporated Compuestos de pirazol utiles como inhibidores de la proteina quinasa.
JP2004521901A (ja) 2001-02-02 2004-07-22 グラクソ　グループ　リミテッド Ｔｇｆ阻害剤としてのピラゾール
MY130778A (en) 2001-02-09 2007-07-31 Vertex Pharma Heterocyclic inhibitiors of erk2 and uses thereof
ES2292753T4 (es) 2001-03-29 2009-02-16 Vertex Pharmaceuticals Incorporated Inhibidores de quinasas n-terminales c-jun (jnk) y otras proteina quinasas.
EP1389206B1 (fr) 2001-04-13 2006-09-13 Vertex Pharmaceuticals Incorporated Inhibiteurs de c-jun n-terminal kinases (jnk) et d'autres proteines kinases
EP1383771A1 (fr) 2001-04-20 2004-01-28 Vertex Pharmaceuticals Incorporated Derives de 9-deazaguanine utilises comme inhibiteurs de la gsk-3
JP4316893B2 (ja) 2001-05-16 2009-08-19 バーテックス ファーマシューティカルズ インコーポレイテッド Ｓｒｃおよび他のプロテインキナーゼのインヒビター
MXPA03010961A (es) 2001-05-31 2004-02-27 Vertex Pharma Compuestos de tiazol utiles como inhibidores de proteinas cinasas.
JP4523271B2 (ja) 2001-06-01 2010-08-11 バーテックス ファーマシューティカルズ インコーポレイテッド プロテインキナーゼのインヒビターとして有用なチアゾール化合物
MXPA03011652A (es) 2001-06-15 2004-05-31 Vertex Pharma 5-(2-aminopirimidin-4-il) benzioxazoles como inhibidores de proteinas cinasa.
ATE337312T1 (de) 2001-07-03 2006-09-15 Vertex Pharma Isoxazolyl-pyrimidines als inhibitoren von src- und lck-protein-kinasen
GB0119865D0 (en) * 2001-08-14 2001-10-10 Cancer Res Campaign Tech DNA-PK inhibitors
CA2469316A1 (fr) 2001-12-07 2003-06-19 Vertex Pharmaceuticals, Inc. Composes a base de pyrimidine utiles en tant qu'inhibiteurs des gsk-3
AU2003215087B2 (en) 2002-02-06 2009-07-16 Vertex Pharmaceuticals Incorporated Heteroaryl compounds useful as inhibitors of GSK-3
US20030199525A1 (en) 2002-03-21 2003-10-23 Hirst Gavin C. Kinase inhibitors
US20030207873A1 (en) 2002-04-10 2003-11-06 Edmund Harrington Inhibitors of Src and other protein kinases
EP1506189A1 (fr) 2002-04-26 2005-02-16 Vertex Pharmaceuticals Incorporated Derives de pyrrole utilises en tant qu'inhibiteurs de erk2 et leurs utilisations
JP4681302B2 (ja) 2002-05-06 2011-05-11 バーテックス ファーマシューティカルズ インコーポレイテッド チアジアゾールまたはオキサジアゾール、およびこれらの、ｊａｋプロテインキナーゼのインヒビターとしての使用
JP2005528443A (ja) 2002-05-30 2005-09-22 バーテックス　ファーマシューティカルズ　インコーポレイテッド Ｊａｋキナーゼおよびｃｄｋ２プロテインキナーゼのインヒビター
MY141867A (en) 2002-06-20 2010-07-16 Vertex Pharma Substituted pyrimidines useful as protein kinase inhibitors
WO2004005283A1 (fr) 2002-07-09 2004-01-15 Vertex Pharmaceuticals Incorporated Imidazoles, oxazoles et thiazoles presentant des activites d'inhibition des proteines kinases
US7304071B2 (en) 2002-08-14 2007-12-04 Vertex Pharmaceuticals Incorporated Protein kinase inhibitors and uses thereof
US7419984B2 (en) 2002-10-17 2008-09-02 Cell Therapeutics, Inc. Pyrimidines and uses thereof
DE60330895D1 (de) 2002-11-01 2010-02-25 Vertex Pharma Verbindungen, die sich als inhibitoren vonjak und anderen proteinkinasen eignen
JP4688498B2 (ja) 2002-11-04 2011-05-25 バーテックス ファーマシューティカルズ インコーポレイテッド Ｊａｋインヒビターとしてのヘテロアリール−ピリミジン誘導体
WO2004058749A1 (fr) 2002-12-18 2004-07-15 Vertex Pharmaceuticals Incorporated Derives de benzisoxazole utiles en tant qu'inhibiteurs des proteine kinases
US7144911B2 (en) 2002-12-31 2006-12-05 Deciphera Pharmaceuticals Llc Anti-inflammatory medicaments
CA2515132C (fr) 2003-02-07 2012-01-03 Vertex Pharmaceuticals Incorporated Pyrroles a substitution heteroaryle servant d'inhibiteurs de proteines kinases
AU2004221881A1 (en) 2003-03-13 2004-09-30 Vertex Pharmaceuticals Incorporated Compositions useful as protein kinase inhibitors
AU2004223866A1 (en) 2003-03-24 2004-10-07 Luitpold Pharmaceuticals, Inc. Xanthones, thioxanthones and acridinones as DNA-PK inhibitors
JP2006524688A (ja) 2003-03-25 2006-11-02 バーテックス　ファーマシューティカルズ　インコーポレイテッド プロテインキナーゼのインヒビターとして有用なチアゾール
US6875781B2 (en) 2003-04-04 2005-04-05 Cell Therapeutics, Inc. Pyridines and uses thereof
US7189724B2 (en) 2003-04-15 2007-03-13 Valeant Research And Development Quinoxaline derivatives having antiviral activity
EP1678147B1 (fr) 2003-09-15 2012-08-08 Lead Discovery Center GmbH Derives d'aminopyrimidine a disubstitution 4,6 actifs sur le plan pharmaceutique en tant que modulateurs des proteine kinases
AU2004313928A1 (en) 2003-12-02 2005-07-28 Vertex Pharmaceuticals, Inc. Heterocyclic protein kinase inhibitors and uses thereof
WO2005056547A2 (fr) 2003-12-04 2005-06-23 Vertex Pharmaceuticals Incorporated Quinoxalines utiles comme inhibiteurs des proteines kinases
TW200533357A (en) 2004-01-08 2005-10-16 Millennium Pharm Inc 2-(amino-substituted)-4-aryl pyrimidines and related compounds useful for treating inflammatory diseases
PT1725233E (pt) 2004-03-15 2011-03-23 Sunesis Pharmaceuticals Inc Composição farmacêutica compreendendo sns-595 e suas utilizações
GB0405985D0 (en) 2004-03-17 2004-04-21 Novartis Forschungsstiftung Kinase
KR20070012555A (ko) 2004-05-14 2007-01-25 버텍스 파마슈티칼스 인코포레이티드 피롤릴피리미딘 ｅｒｋ 단백질 키나제 억제제의 프로드럭
JP4449580B2 (ja) 2004-05-31 2010-04-14 宇部興産株式会社 ４−アラルキルアミノピリミジン誘導体及び抗菌剤
CA2568451A1 (fr) 2004-06-04 2005-12-22 Arena Pharmaceuticals, Inc. Derives d'aryle et d'heteroaryle substitues tenant lieu de modulateurs du metabolisme et prevention et traitement de troubles associes
ES2359007T3 (es) 2004-09-17 2011-05-17 Vertex Pharmaceuticals Incorporated Compuestos de diaminotriazol útiles como inhibidores de proteínas quinasas.
US9611230B2 (en) 2004-10-13 2017-04-04 Ptc Therapeutics, Inc. 1,3,4-oxadiazole benzoic acid compounds and their use for nonsense suppression and the treatment of disease
AU2005293384A1 (en) 2004-10-15 2006-04-20 Astrazeneca Ab Quinoxalines as B Raf inhibitors
GT200500284A (es) 2004-10-15 2006-03-27 Aventis Pharma Inc Pirimidinas como antagonistas del receptor de prostaglandina d2
US20060166936A1 (en) 2004-10-29 2006-07-27 Hayley Binch Diaminotriazole compounds useful as inhibitors of protein kinases
US7517870B2 (en) 2004-12-03 2009-04-14 Fondazione Telethon Use of compounds that interfere with the hedgehog signaling pathway for the manufacture of a medicament for preventing, inhibiting, and/or reversing ocular diseases related with ocular neovascularization
CA2590250A1 (fr) 2004-12-14 2006-06-22 Vertex Pharmaceuticals Incorporated Inhibiteurs de la proteine kinase erk et utilisations
EP1833820A1 (fr) 2004-12-23 2007-09-19 Vertex Pharmaceuticals Incorporated Inhibiteurs selectifs de la proteine kinase erk et leurs utilisations
AU2006210513C1 (en) 2005-02-04 2012-10-25 Senomyx, Inc. Compounds comprising linked heteroaryl moieties and their use as novel umami flavor modifiers, tastants and taste enhancers for comestible compositions
RU2007140733A (ru) 2005-04-06 2009-05-20 Айрм Ллк (Bm) Диариламинсодержащие соединения и композиции, и их применение в качестве модуляторов ядерных рецепторов стероидного гормона
AR054438A1 (es) 2005-04-15 2007-06-27 Kudos Pharm Ltd Inhibidores de adn -pk
JP2008542219A (ja) 2005-05-25 2008-11-27 インゲニウム ファーマシューティカルズ ジーエムビーエイチ 疼痛処置法
WO2006138418A2 (fr) 2005-06-14 2006-12-28 President And Fellows Of Harvard College Amelioration de la performance cognitive avec des activateurs de sirtuine
JP2007008045A (ja) 2005-06-30 2007-01-18 Mitsui Chemicals Inc 光記録媒体および１ｈ−キノキサリン−２−オン誘導体
WO2007014250A2 (fr) 2005-07-26 2007-02-01 Vertex Pharmaceuticals Incorporated Inhibition de kinase d'abl
GB0520657D0 (en) 2005-10-11 2005-11-16 Ludwig Inst Cancer Res Pharmaceutical compounds
JP2009514875A (ja) 2005-11-02 2009-04-09 サイトキネティクス・インコーポレーテッド 化学物質、組成物、および方法
BRPI0619704A2 (pt) 2005-11-03 2011-10-11 Vertex Pharma composto, composição, método para inibir a atividade da proteìna aurora quinase numa amostra biológica, método para tratar um distúrbio proliferativo e método para tratar cáncer
EP1951716B1 (fr) 2005-11-16 2011-05-04 Vertex Pharmaceuticals, Inc. Aminopyrimidines utiles en tant qu inhibiteurs de la kinase
EP1983823A1 (fr) 2006-01-17 2008-10-29 VIB vzw Inhibiteurs de la prolyl-hydroxylase 1 pour le traitement de la degenerescence des muscles du squelette
JO2660B1 (en) 2006-01-20 2012-06-17 نوفارتيس ايه جي Pi-3 inhibitors and methods of use
PE20071025A1 (es) 2006-01-31 2007-10-17 Mitsubishi Tanabe Pharma Corp Compuesto amina trisustituido
US8013153B2 (en) 2006-03-23 2011-09-06 Janssen Pharmaceutica, N.V. Substituted pyrimidine kinase inhibitors
US20080280891A1 (en) 2006-06-27 2008-11-13 Locus Pharmaceuticals, Inc. Anti-cancer agents and uses thereof
WO2008008852A2 (fr) 2006-07-11 2008-01-17 Emory University Antagonistes de cxcr4 comprenant des hétéroatomes pour le traitement de troubles médicaux
TW200811134A (en) 2006-07-12 2008-03-01 Irm Llc Compounds and compositions as protein kinase inhibitors
PE20121506A1 (es) 2006-07-14 2012-11-26 Amgen Inc Compuestos triazolopiridinas como inhibidores de c-met
AU2007271964B2 (en) 2006-07-14 2012-01-19 Novartis Ag Pyrimidine derivatives as ALK-5 inhibitors
US7635683B2 (en) 2006-08-04 2009-12-22 Enanta Pharmaceuticals, Inc. Quinoxalinyl tripeptide hepatitis C virus inhibitors
US8541428B2 (en) 2006-08-22 2013-09-24 Technion Research And Development Foundation Ltd. Heterocyclic derivatives, pharmaceutical compositions and methods of use thereof
EP1903038A1 (fr) 2006-09-07 2008-03-26 Bayer Schering Pharma Aktiengesellschaft Dérivés N-(1-hetaryl-piperidine-4-yl)-(het)arylamide utilisées comme modulateurs du recepteur EP2
US7875603B2 (en) 2006-09-21 2011-01-25 Nova Southeastern University Specific inhibitors for vascular endothelial growth factor receptors
KR101101675B1 (ko) 2006-10-02 2011-12-30 노파르티스 아게 단백질 키나제 억제제로서의 화합물 및 조성물
DE102006050512A1 (de) 2006-10-26 2008-04-30 Bayer Healthcare Ag Substituierte heterocyclische Verbindungen und ihre Verwendung
JP2010509231A (ja) 2006-11-02 2010-03-25 バーテックス ファーマシューティカルズ インコーポレイテッド プロテインキナーゼの阻害剤として有用なアミノピリジンおよびアミノピリミジン
CN101679371A (zh) 2006-12-04 2010-03-24 艾美罗股份公司 作为腺苷受体拮抗剂的取代的嘧啶
CA2673353A1 (fr) 2006-12-19 2008-06-26 Vertex Pharmaceuticals Incorporated Aminopyridines utiles comme inhibiteurs de proteine kinases
AU2007341997A1 (en) 2006-12-28 2008-07-10 Ambrx, Inc. Phenazine and quinoxaline substituted amino acids and polypeptides
WO2008092199A1 (fr) 2007-01-31 2008-08-07 Cytopia Research Pty Ltd Composés à base de thiopyrimidine et ses utilisations
WO2008106202A1 (fr) 2007-02-27 2008-09-04 Housey Gerard M Modulateurs de théramutéine
WO2008112651A2 (fr) 2007-03-09 2008-09-18 Vertex Pharmaceuticals Incorporated Aminopyrimidines utiles en tant qu'inhibiteurs des protéines kinases
EP2134709A1 (fr) 2007-03-09 2009-12-23 Vertex Pharmaceuticals, Inc. Utilisation des aminopyridines comme inhibiteurs de protéines kinases
CA2679884A1 (fr) 2007-03-09 2008-09-18 Vertex Pharmaceuticals Incorporated Aminopyrimidines utiles en tant qu'inhibiteurs des proteines kinases
WO2008115973A2 (fr) 2007-03-20 2008-09-25 Vertex Pharmaceuticals Incorporated Aminopyrimidines utiles en tant qu'inhibiteurs de kinase
DE102007015169A1 (de) 2007-03-27 2008-10-02 Universität des Saarlandes Campus Saarbrücken 17Beta-Hydroxysteroid-Dehydrogenase-Typ1-Inhibitoren zur Behandlung hormonabhängiger Erkrankungen
NZ580343A (en) 2007-04-13 2012-03-30 Vertex Pharma Aminopyrimidines useful as kinase inhibitors
US7910587B2 (en) 2007-04-26 2011-03-22 Enanta Pharmaceuticals, Inc. Quinoxalinyl dipeptide hepatitis C virus inhibitors
MX2009011811A (es) 2007-05-02 2010-01-14 Vertex Pharma Aminopirimidinas utiles como inhibidores de cinasa.
WO2008137621A1 (fr) 2007-05-02 2008-11-13 Vertex Pharmaceuticals Incorporated Aminopyrimidines servant d'inhibiteurs de kinases
MX2009011810A (es) 2007-05-02 2010-01-14 Vertex Pharma Tiazoles y pirazoles utiles como inhibidores de cinasa.
US20100234386A1 (en) 2007-05-10 2010-09-16 Chaudhari Amita Quinoxaline derivatives as pi3 kinase inhibitors
WO2008144253A1 (fr) 2007-05-14 2008-11-27 Irm Llc Inhibiteurs de la protéine kinase et procédé d'utilisation de ceux-ci
JP2010528021A (ja) 2007-05-24 2010-08-19 バーテックス ファーマシューティカルズ インコーポレイテッド キナーゼのインヒビターとして有用なチアゾールおよびピラゾール
AU2008257559B2 (en) 2007-05-25 2013-10-10 AbbVie Deutschland GmbH & Co. KG Heterocyclic compounds as positive modulators of metabotropic glutamate receptor 2 (MGLU2 receptor)
US8685962B2 (en) 2007-07-02 2014-04-01 Technion Research & Development Foundation Limited Compositions, articles and methods comprising TSPO ligands for preventing or reducing tobacco-associated damage
WO2009008991A2 (fr) 2007-07-06 2009-01-15 Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services National Institutes Of Health Modulation de la régulation d'énergie et de la fonction cérébrale par adn-pkcs
UY31232A1 (es) 2007-07-19 2009-03-02 Compuestos derivados de dibenzotifenilamino-cromen-4-onas activas sustituidas y sus isomeros y aplicaciones
BRPI0813863B1 (pt) 2007-08-01 2016-09-27 Ihara Chemical Ind Co derivado de oxopirazina ou um sal agroquimicamente aceitável do mesmo, herbicida, e, método para usar um herbicida
EP2190466A4 (fr) 2007-08-10 2011-12-21 Burnham Inst Medical Research Activateurs de la phosphatase alcaline non spécifique des tissus (tnap) et leurs utilisations
DE102007044032A1 (de) 2007-09-14 2009-03-19 Bayer Healthcare Ag Substituierte heterocyclische Verbindungen und ihre Verwendung
ATE510827T1 (de) 2007-10-12 2011-06-15 Ingenium Pharmaceuticals Gmbh Inhibitoren von proteinkinasen
WO2009061761A2 (fr) 2007-11-06 2009-05-14 E. I. Du Pont De Nemours And Company Amines fongicides
WO2009091388A2 (fr) 2007-12-21 2009-07-23 Progenics Pharmaceuticals, Inc. Triazines et composés associés présentant une activité antivirale, compositions et procédés associés
WO2009105220A1 (fr) 2008-02-19 2009-08-27 Janssen Pharmaceutica N.V. Aryl-hydroxyéthylamino-pyrimidines et triazines en tant que modulateurs d'amide d'acide gras hydrolase
WO2009107391A1 (fr) 2008-02-27 2009-09-03 武田薬品工業株式会社 Composé contenant un cycle aromatique à 6 chaînons
MX2010009576A (es) 2008-03-05 2010-09-24 Merck Patent Gmbh Derivados de quinoxalinona como estimulantes de la secrecion de insulina, metodos para obtenerlos y su uso en el tratamiento de la diabetes.
US8268834B2 (en) 2008-03-19 2012-09-18 Novartis Ag Pyrazine derivatives that inhibit phosphatidylinositol 3-kinase enzyme
US20110065739A1 (en) 2008-06-02 2011-03-17 Makoto Ishikawa Novel isoxazole drivative
AU2009259754B2 (en) 2008-06-16 2014-10-02 Merck Patent Gmbh Quinoxalinedione derivatives
EP2138488A1 (fr) 2008-06-26 2009-12-30 sanofi-aventis Dérivés de 4-(pyridin-4-yl)-1H-[1,3,5]triazin-2-ones comme inhibiteurs de GSK3-beta utiles pour le traitement de maladies neurodégénératives
ES2402087T3 (es) 2008-07-23 2013-04-26 Vertex Pharmaceuticals Incorporated Inhibidores de la pirazolopiridina quinasa
WO2010048149A2 (fr) 2008-10-20 2010-04-29 Kalypsys, Inc. Modulateurs hétérocycliques de gpr119 pour le traitement d'une maladie
UY32251A (es) 2008-11-20 2010-05-31 Glaxosmithkline Llc Compuestos quimicos
WO2010065899A2 (fr) 2008-12-05 2010-06-10 Molecular Insight Pharmaceuticals, Inc. Complexes de technétium- et rhénium-bis (hétéroaryles) et leurs procédés d'utilisation
RS56995B1 (sr) 2008-12-19 2018-05-31 Vertex Pharma Derivati pirazina korisni kao inhibitori atr kinaze
WO2010093808A1 (fr) 2009-02-11 2010-08-19 Reaction Biology Corp. Inhibiteurs de kinase sélectifs
JP2010111702A (ja) 2009-02-16 2010-05-20 Tetsuya Nishio 複素環化合物、その製造法および用途
WO2011022348A1 (fr) 2009-08-18 2011-02-24 Janssen Pharmaceutica Nv Modulateurs d'éthylène diamine d'une amide hydrolase d'acide gras
AR077999A1 (es) 2009-09-02 2011-10-05 Vifor Int Ag Antagonistas de pirimidin y triazin-hepcidina
EP2947073B1 (fr) 2009-10-22 2019-04-03 Fibrotech Therapeutics Pty Ltd Analogues cycliques fusionnés d'agents antifibrotiques
ES2360333B1 (es) 2009-10-29 2012-05-04 Consejo Superior De Investigaciones Cientificas (Csic) (70%) Derivados de bis (aralquil) amino y sistemas (hetero) aromaticos de seis miembros y su uso en el tratamiento de patologias neurodegenerativas, incluida la enfermedad de alzheimer
EP2495238A4 (fr) 2009-10-30 2013-04-24 Mochida Pharm Co Ltd Nouveau dérivé de 3-hydroxy-5-arylisoxazole
WO2011078371A1 (fr) 2009-12-25 2011-06-30 持田製薬株式会社 Nouveau dérivé 3-hydroxy-5-arylisothiazole
UY33213A (es) 2010-02-18 2011-09-30 Almirall Sa Derivados de pirazol como inhibidores de jak
JP2013522249A (ja) 2010-03-16 2013-06-13 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング モルホリニルキナゾリン
TWI516264B (zh) 2010-05-06 2016-01-11 臺北醫學大學 芳香醯喹啉化合物
JP2011246389A (ja) * 2010-05-26 2011-12-08 Oncotherapy Science Ltd Ｔｔｋ阻害作用を有する縮環ピラゾール誘導体
DE102010025786A1 (de) 2010-07-01 2012-01-05 Merck Patent Gmbh Pyrazolochinoline
DE102010035744A1 (de) 2010-08-28 2012-03-01 Merck Patent Gmbh Imidazolonylchinoline
WO2012129562A2 (fr) 2011-03-24 2012-09-27 The Scripps Research Institute Composés et procédés pour l'induction de la chondrogenèse
GB201114051D0 (en) 2011-08-15 2011-09-28 Domainex Ltd Compounds and their uses
ES2725790T3 (es) 2011-08-26 2019-09-27 Neupharma Inc Algunas entidades químicas, composiciones, y métodos
CN108794411B (zh) 2011-09-14 2022-06-07 润新生物公司 某些化学实体、组合物及方法
US9249110B2 (en) 2011-09-21 2016-02-02 Neupharma, Inc. Substituted quinoxalines as B-raf kinase inhibitors
US9249111B2 (en) 2011-09-30 2016-02-02 Neupharma, Inc. Substituted quinoxalines as B-RAF kinase inhibitors
DE102011118830A1 (de) 2011-11-18 2013-05-23 Merck Patent Gmbh Morpholinylbenzotriazine
GB201120993D0 (en) 2011-12-06 2012-01-18 Imp Innovations Ltd Novel compounds and their use in therapy
WO2013112950A2 (fr) 2012-01-25 2013-08-01 Neupharma, Inc. Entités chimiques particulières, compositions et procédés
SI2841428T1 (sl) 2012-04-24 2018-12-31 Vertex Pharmaceuticals Incorporated Inhibitorji DNA-PK
US9725421B2 (en) 2012-11-12 2017-08-08 Neupharma, Inc. Substituted quinoxalines as B-raf kinase inhibitors
CN107200749B (zh) 2013-03-12 2019-09-03 沃泰克斯药物股份有限公司 Dna-pk抑制剂
EP3057953B1 (fr) 2013-10-17 2018-08-15 Vertex Pharmaceuticals Incorporated Co-cristaux de (s)-n-méthyl-8-(1-((2'-méthyl-[4,5'-bipyrimidin]-6-yl)amino)propan-2-yl)quinoline-4-carboxamide et leurs dérivés deutérés utilisés comme inhibiteurs de protéine kinase dépendante de l'adn (dna-pk)

Also Published As

Publication number Publication date
JP2018135389A (ja) 2018-08-30
EP3527563A1 (fr) 2019-08-21
LT2970218T (lt) 2019-03-12
RU2676259C2 (ru) 2018-12-27
US9987284B2 (en) 2018-06-05
ES2900061T3 (es) 2022-03-15
US20180311254A1 (en) 2018-11-01
CN107200749A (zh) 2017-09-26
RU2015143211A (ru) 2017-04-18
EP3527563B1 (fr) 2021-09-01
US20160354381A1 (en) 2016-12-08
CA2904641A1 (fr) 2014-10-02
KR102216284B1 (ko) 2021-02-18
CY1125436T1 (el) 2023-03-24
HK1220190A1 (zh) 2017-04-28
PT3527563T (pt) 2021-12-09
AU2014244555B2 (en) 2018-06-28
SI2970218T1 (sl) 2019-04-30
HUE041544T2 (hu) 2019-05-28
PT2970218T (pt) 2019-03-01
NZ712576A (en) 2020-11-27
US20140275059A1 (en) 2014-09-18
US9340557B2 (en) 2016-05-17
HRP20190373T1 (hr) 2019-04-19
US9359380B2 (en) 2016-06-07
US20230277547A1 (en) 2023-09-07
WO2014159690A1 (fr) 2014-10-02
DK3527563T3 (da) 2021-12-06
AU2018236800A1 (en) 2018-10-25
PL3527563T3 (pl) 2022-03-07
SI3527563T1 (sl) 2022-01-31
US20140275024A1 (en) 2014-09-18
US20190255062A1 (en) 2019-08-22
EP2970218A1 (fr) 2016-01-20
ES2711839T3 (es) 2019-05-07
BR112015021888A8 (pt) 2019-11-26
US20180161336A1 (en) 2018-06-14
BR112015021888B1 (pt) 2022-08-09
CN107200749B (zh) 2019-09-03
HRP20211855T1 (hr) 2022-03-04
EP2970218B1 (fr) 2018-11-28
CN105246883A (zh) 2016-01-13
BR112015021888A2 (pt) 2017-07-18
US10258627B2 (en) 2019-04-16
AU2018236800B2 (en) 2020-04-09
US20210069203A1 (en) 2021-03-11
CN105246883B (zh) 2017-07-21
CA2904641C (fr) 2021-07-20
RS62649B1 (sr) 2021-12-31
LT3527563T (lt) 2021-12-10
ME03336B (fr) 2019-10-20
US11813267B2 (en) 2023-11-14
US20210236505A1 (en) 2021-08-05
EP3985003B1 (fr) 2023-08-09
EP3985003C0 (fr) 2023-08-09
RU2015143211A3 (fr) 2018-03-06
IL241330A0 (en) 2015-11-30
TR201901886T4 (tr) 2019-03-21
JP2016516706A (ja) 2016-06-09
KR20150126051A (ko) 2015-11-10
MX365294B (es) 2019-05-29
AU2014244555A1 (en) 2015-10-15
EP3985003A1 (fr) 2022-04-20
DK2970218T3 (en) 2019-03-25
SG11201507203RA (en) 2015-10-29
IL241330B (en) 2021-05-31
MX2015012502A (es) 2015-12-16
US20160340341A1 (en) 2016-11-24
HUE057527T2 (hu) 2022-05-28
US10786512B2 (en) 2020-09-29
PL2970218T3 (pl) 2019-05-31
CY1121360T1 (el) 2020-05-29
RS58374B1 (sr) 2019-03-29
US20190290654A1 (en) 2019-09-26
US10973830B2 (en) 2021-04-13
JP6360878B2 (ja) 2018-07-18

Similar Documents

Publication Publication Date Title
HRP20190373T1 (hr) Inhibitori dnk-pk
HUE037516T2 (hu) DNS-PK inhibitorok
EP2968276A4 (fr) Inhibiteurs hybrides de la nécroptose
EP3082809A4 (fr) Inhibiteurs de btk
HK1211578A1 (en) Amidoimidazopyridazines as mknk-1 kinase inhibitors mknk-1
HK1216531A1 (zh) 新的抑制劑
EP3082811A4 (fr) Inhibiteurs de btk
EP3003372A4 (fr) Inhibiteurs du facteur h du complément
EP2994124A4 (fr) Inhibiteurs d'enzymes métallo-ss-lactamase
IL246230A0 (en) Amines thf quinazoline as pde1 inhibitors
EP3071572A4 (fr) Inhibiteurs de protéines kinases
EP2994143A4 (fr) Inhibiteurs de stat6
HK1213885A1 (zh) 作為 抑制劑的咪唑並-三嗪衍生物
EP3074401A4 (fr) Inhibiteurs de protéines kinases
EP2968324A4 (fr) Dérivés de pyridizinone substitués en tant qu'inhibiteurs de pde10
EP3082810A4 (fr) Inhibiteurs d'erk
EP3071573A4 (fr) Inhibiteurs de protéines kinases
EP2945930A4 (fr) Nouveaux inhibiteurs de ddp-iv
AU2013901594A0 (en) Ai

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20151002

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: EXAMINATION IS IN PROGRESS

17Q First examination report despatched

Effective date: 20161213

REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 1220190

Country of ref document: HK

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: GRANT OF PATENT IS INTENDED

INTG Intention to grant announced

Effective date: 20170531

GRAJ Information related to disapproval of communication of intention to grant by the applicant or resumption of examination proceedings by the epo deleted

Free format text: ORIGINAL CODE: EPIDOSDIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: EXAMINATION IS IN PROGRESS

INTC Intention to grant announced (deleted)
GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: GRANT OF PATENT IS INTENDED

INTG Intention to grant announced

Effective date: 20180606

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE PATENT HAS BEEN GRANTED

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: AT

Ref legal event code: REF

Ref document number: 1070068

Country of ref document: AT

Kind code of ref document: T

Effective date: 20181215

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602014036896

Country of ref document: DE

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: RO

Ref legal event code: EPE

REG Reference to a national code

Ref country code: HR

Ref legal event code: TUEP

Ref document number: P20190373

Country of ref document: HR

RAP2 Party data changed (patent owner data changed or rights of a patent transferred)

Owner name: VERTEX PHARMACEUTICALS INC.

REG Reference to a national code

Ref country code: PT

Ref legal event code: SC4A

Ref document number: 2970218

Country of ref document: PT

Date of ref document: 20190301

Kind code of ref document: T

Free format text: AVAILABILITY OF NATIONAL TRANSLATION

Effective date: 20190225

RAP2 Party data changed (patent owner data changed or rights of a patent transferred)

Owner name: VERTEX PHARMACEUTICALS INCORPORATED

REG Reference to a national code

Ref country code: CH

Ref legal event code: PK

Free format text: BERICHTIGUNG B8

REG Reference to a national code

Ref country code: DK

Ref legal event code: T3

Effective date: 20190318

REG Reference to a national code

Ref country code: SE

Ref legal event code: TRGR

REG Reference to a national code

Ref country code: NL

Ref legal event code: FP

REG Reference to a national code

Ref country code: EE

Ref legal event code: FG4A

Ref document number: E016962

Country of ref document: EE

Effective date: 20190222

REG Reference to a national code

Ref country code: HR

Ref legal event code: T1PR

Ref document number: P20190373

Country of ref document: HR

REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Ref document number: 2711839

Country of ref document: ES

Kind code of ref document: T3

Effective date: 20190507

REG Reference to a national code

Ref country code: NO

Ref legal event code: T2

Effective date: 20181128

REG Reference to a national code

Ref country code: HU

Ref legal event code: AG4A

Ref document number: E041544

Country of ref document: HU

REG Reference to a national code

Ref country code: GR

Ref legal event code: EP

Ref document number: 20190400648

Country of ref document: GR

Effective date: 20190509

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 602014036896

Country of ref document: DE

REG Reference to a national code

Ref country code: HR

Ref legal event code: ODRP

Ref document number: P20190373

Country of ref document: HR

Payment date: 20190402

Year of fee payment: 6

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed

Effective date: 20190829

REG Reference to a national code

Ref country code: HR

Ref legal event code: ODRP

Ref document number: P20190373

Country of ref document: HR

Payment date: 20200226

Year of fee payment: 7

REG Reference to a national code

Ref country code: HR

Ref legal event code: ODRP

Ref document number: P20190373

Country of ref document: HR

Payment date: 20210223

Year of fee payment: 8

REG Reference to a national code

Ref country code: HR

Ref legal event code: ODRP

Ref document number: P20190373

Country of ref document: HR

Payment date: 20220221

Year of fee payment: 9

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: MK

Payment date: 20220221

Year of fee payment: 9

REG Reference to a national code

Ref country code: HR

Ref legal event code: ODRP

Ref document number: P20190373

Country of ref document: HR

Payment date: 20230221

Year of fee payment: 10

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: SM

Payment date: 20230223

Year of fee payment: 10

Ref country code: RO

Payment date: 20230227

Year of fee payment: 10

Ref country code: NO

Payment date: 20230329

Year of fee payment: 10

Ref country code: MC

Payment date: 20230222

Year of fee payment: 10

Ref country code: LU

Payment date: 20230327

Year of fee payment: 10

Ref country code: LT

Payment date: 20230220

Year of fee payment: 10

Ref country code: IE

Payment date: 20230327

Year of fee payment: 10

Ref country code: FR

Payment date: 20230327

Year of fee payment: 10

Ref country code: FI

Payment date: 20230327

Year of fee payment: 10

Ref country code: DK

Payment date: 20230329

Year of fee payment: 10

Ref country code: CZ

Payment date: 20230301

Year of fee payment: 10

Ref country code: BG

Payment date: 20230322

Year of fee payment: 10

Ref country code: AT

Payment date: 20230221

Year of fee payment: 10

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: TR

Payment date: 20230224

Year of fee payment: 10

Ref country code: SK

Payment date: 20230220

Year of fee payment: 10

Ref country code: SI

Payment date: 20230221

Year of fee payment: 10

Ref country code: SE

Payment date: 20230315

Year of fee payment: 10

Ref country code: RS

Payment date: 20230221

Year of fee payment: 10

Ref country code: PT

Payment date: 20230222

Year of fee payment: 10

Ref country code: PL

Payment date: 20230221

Year of fee payment: 10

Ref country code: LV

Payment date: 20230222

Year of fee payment: 10

Ref country code: IT

Payment date: 20230321

Year of fee payment: 10

Ref country code: IS

Payment date: 20230220

Year of fee payment: 10

Ref country code: HU

Payment date: 20230303

Year of fee payment: 10

Ref country code: HR

Payment date: 20230221

Year of fee payment: 10

Ref country code: GR

Payment date: 20230331

Year of fee payment: 10

Ref country code: GB

Payment date: 20230327

Year of fee payment: 10

Ref country code: EE

Payment date: 20230220

Year of fee payment: 10

Ref country code: DE

Payment date: 20230329

Year of fee payment: 10

Ref country code: CY

Payment date: 20230222

Year of fee payment: 10

Ref country code: BE

Payment date: 20230327

Year of fee payment: 10

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: NL

Payment date: 20230326

Year of fee payment: 10

Ref country code: MT

Payment date: 20230220

Year of fee payment: 10

P01 Opt-out of the competence of the unified patent court (upc) registered

Effective date: 20230528

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: ES

Payment date: 20230403

Year of fee payment: 10

Ref country code: CH

Payment date: 20230402

Year of fee payment: 10

REG Reference to a national code

Ref country code: AT

Ref legal event code: UEP

Ref document number: 1070068

Country of ref document: AT

Kind code of ref document: T

Effective date: 20181128

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: AL

Payment date: 20230307

Year of fee payment: 10

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: MK

Payment date: 20230221

Year of fee payment: 10

REG Reference to a national code

Ref country code: HR

Ref legal event code: ODRP

Ref document number: P20190373

Country of ref document: HR

Payment date: 20240221

Year of fee payment: 11

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GR

Payment date: 20240327

Year of fee payment: 11

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: IS

Payment date: 20240228

Year of fee payment: 11

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: LT

Payment date: 20240220

Year of fee payment: 11

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: LU

Payment date: 20240327

Year of fee payment: 11

Ref country code: IE

Payment date: 20240327

Year of fee payment: 11

Ref country code: NL

Payment date: 20240326

Year of fee payment: 11